Age-dependent renal cortical microvascular loss in female mice

Victor H. Urbieta-Caceres, Farhan A. Syed, Jing Lin, Xiang Yang Zhu, Kyra L. Jordan, Caitlin C. Bell, Michael D. Bentley, Amir Lerman, Sundeep Khosla, Lilach O. Lerman

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 μm) was decreased in all aged groups compared with young controls (30.3 5.8 vessels/mm 2, P<0.05), but tended to be lower in sham compared with Ovx and Ovx E (9.9±1.7 vs. 17.2±4.2 and 18±3.0 vessels/mm 2, P 0.08 and P 0.02, respectively). Cortical density of larger microvessels (200-500 μm) decreased only in aged sham (P 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx E, in association with downregulated transforming growth factor-signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis.

Original languageEnglish (US)
Pages (from-to)E979-E986
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number8
DOIs
StatePublished - Apr 15 2012

Keywords

  • Aging
  • Estrogen
  • Kidney

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Age-dependent renal cortical microvascular loss in female mice'. Together they form a unique fingerprint.

  • Cite this